Prion Disease Database (PDDB)

Category Cross-Omics>Knowledge Bases/Databases/Tools and Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools

Abstract The Prion Disease Database (PDDB) is a public database that supports the ‘prion disease’ research community by collecting, integrating, and presenting data from public sources and collaborating laboratories.

The PDDB is a web-based resource for research in prion disease and also for potential use in research on other complex human diseases.

It contains time-course data from over 450 microarrays and histoblots showing temporal PrPSc accumulation ‘patterns in brains’ from eight mouse-prion strain combinations, as well as basic data exploration tools and ‘systems biology’ tools.

The integration of data and tools in the PDDB helps scientists explore relationships in the data efficiently and collectively evaluate the data.

This will make it easier to formulate or cross-check quickly both knowledge-driven hypotheses and hypotheses generated from the data in individual laboratories about key factors involved in fundamental cellular events occurring during the progress of prion disease using both the data and the tools of the PDDB.

The key tools integrated into the PDDB are:

1) A search function coupled with two (2) visualization tools (heat-map and profile viewers) enabling efficient exploration of temporal ‘gene expression patterns’ for sets of genes (e.g. a set of differentially expressed genes);

2) Tools for ‘network analyses’ linking the sets of genes to protein interactions via Cytoscape (see G6G Abstract Number 20092) and its plug-ins and statistical and other systems biology tools supporting the Gaggle interface (see G6G Abstract Number 20222);

3) ‘Web-interfaces’ linking the genes of interest to comprehensive annotations such as NCBI gene page information and KEGG pathways as well as ‘tissue specificity’ information; and

4) A function to construct and store user-defined sets of genes allowing the users of the PDDB, to employ the tools and data of the PDDB for their own research questions.

Collectively, the ‘temporal gene expression’ and histoblot data and the suite of tools support diverse types of studies:

From simple studies inferring ‘gene expression’ levels for a particular set of genes to comprehensive systems biology studies involving integration of data from the PDDB with new data and network analysis of the integrated data.

Construction and maintenance of gene sets --

Regular users of the PDDB have the option to create a user account to get access to the My PDDB feature. This feature enables the creation of sets of genes that can be used for instance to ‘search the expression data’ or to generate a hypothetical ‘protein interaction network’ for exploration in Cytoscape.

Through the My PDDB interface the user may examine and edit user- defined and the public pre-defined lists. This feature is useful to store the results of analyses such as the manufacturer has done for example with the top differentially expressed genes in their study.

Alternatively, genes involved in a certain pathway or biological process can be stored as a set as well as ‘collections of genes’ that are the result of an analysis performed by the user.

While the manufacturer's sets of top differentially expressed genes are publicly available the sets created by users are private but can be made public if desired.

In future sessions the user will then be able to quickly retrieve previously created sets of genes and corresponding expression profiles or interaction networks. This contributes greatly to more efficient data exploration and analysis with the PDDB.

Overview and features of the web interface of the PDDB --

The goal of the PDDB is to provide Not only fundamental dynamic molecular and histological data, but also ‘data exploration tools’ for generation of network-driven hypotheses in ‘systems biology’ research on prion diseases.

The web interface of the PDDB provides several entry points to the data contained in the database.

In the Search submenu, the menu item Microarray Data provides access to advanced search interfaces for ‘gene expression patterns’ across the whole collection of time-course microarray data.

To facilitate the search, the PDDB also provides Connect the Dots, a GDxBase tool that can convert one type of gene or protein identifier into another to be used for the search.

The Download submenu provides access to raw gene expression data files (Affymetrix CEL files).

The Analysis & Tools section gives an overview of several computational and ‘network analysis tools’ that can be employed to investigate functional roles of a set of genes using biological networks.

The tools are categorized as follows:

1) Network Analysis - Cytoscape and BioTapestry (see G6G Product Number 20385) to analyze protein and gene regulatory networks (GRNs), respectively;

2) Pathway Analysis - DAVID (see G6G Abstract Number 20263) for ‘pathway enrichment’ analysis and KEGG for pathway exploration;

3) Visualization and Statistical Analysis - Mayday (a microarray data analysis workbench) and Prequips (see G6G Abstract Number 20407) to visualize and analyze gene expression and proteomics data, respectively; and

4) Transcription Factor Analysis- MotifMogul for in silico gene regulatory network analysis. [MotifMogul is a software tool for predicting transcription factor binding sites using experimentally verified Position Weight Matrices (PWMs)].

Also, a brief overview of the history, background and pathology of prion disease as well as ‘mouse brain histoblots’ are provided in the Prion Disease section.

The Research section contains additional details on the manufacturer’s systems biology approach to prion diseases.

The My PDDB section allows users to create an account where they can store their own sets of genes and use them to explore the data in the PDDB more efficiently.

Network reconstruction and Exploration tools --

The PDDB provides access to tools for reconstruction and exploration of ‘hypothetical networks’ describing essential cellular processes implicated in prion diseases, leading to generation of ‘network-driven hypotheses’ about fundamental principles of prion pathogenesis.

The PDDB provides access to two (2) tools for network analysis; Cytoscape and BioTapestry (as stated above...).

Instead of reconstructing a hypothetical network for a user-defined set of genes, the PDDB also provides three (3) ‘predefined networks’ closely related to prion pathogenesis:

1) Glial Activation,

2) PrPSc Accumulation and

3) Neurodegeneration networks.

For example, a Glial Activation network which contains immune responses to PrPSc accumulation, including complement activation, Cytokines/Chemokines, and cell adhesion molecules.

These predefined networks can serve as platform networks that can be expanded further into more comprehensive networks using Cytoscape plug-ins [cPath (see G6G Abstract Number 20098) and MiMI (see G6G Abstract Number 20311)].

Using Cytoscape plug-ins, the PDDB allows you to perform various types of network exploration, such as; a hypothetical network reconstructed using a set of genes - via:

1) Gene Ontology (GO) enrichment analysis for all ‘network nodes’ using BiNGO (see G6G Abstract Number 20281);

2) Clustering of network nodes using MCODE to identify network modules. [MCODE is a Cytoscape plug-in that finds clusters (highly interconnected regions) in a network.

Clusters mean different things in different types of networks. For instance, clusters in a protein-protein interaction (PPI) network are often protein complexes and parts of pathways, while clusters in a ‘protein similarity network’ represent protein families];

3) Identification of active network modules using jActiveModules. [JActiveModules is a Cytoscape plug-in that searches a ‘molecular interaction network’ to find expression activated subnetworks, i.e., modules]; and

4) Expansion of an existing network using MiMI.

Statistical and systems biology analysis using external tools integrated into the PDDB via the Gaggle --

The integration of the PDDB into the Gaggle environment allows the users to directly exchange data between wide ranges of systems biology applications.

The Gaggle makes exploration of complex, heterogeneous data sets more efficient and enables the user to analyze the data within the PDDB with ‘external analysis tools’ without any administrative overhead such as reformatting of data files.

System Requirements

Web-based.

Manufacturer

Manufacturer Web Site Prion Disease Database (PDDB)

Price Contact manufacturer.

G6G Abstract Number 20544

G6G Manufacturer Number 104159